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Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic tra...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559755/ https://www.ncbi.nlm.nih.gov/pubmed/36229064 http://dx.doi.org/10.26508/lsa.202201496 |
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author | Muslimov, Ilham A Berardi, Valerio Stephenson, Stacy Ginzler, Ellen M Hanly, John G Tiedge, Henri |
author_facet | Muslimov, Ilham A Berardi, Valerio Stephenson, Stacy Ginzler, Ellen M Hanly, John G Tiedge, Henri |
author_sort | Muslimov, Ilham A |
collection | PubMed |
description | Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood–brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus. |
format | Online Article Text |
id | pubmed-9559755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-95597552022-10-14 Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus Muslimov, Ilham A Berardi, Valerio Stephenson, Stacy Ginzler, Ellen M Hanly, John G Tiedge, Henri Life Sci Alliance Research Articles Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood–brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus. Life Science Alliance LLC 2022-10-13 /pmc/articles/PMC9559755/ /pubmed/36229064 http://dx.doi.org/10.26508/lsa.202201496 Text en © 2022 Muslimov et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Muslimov, Ilham A Berardi, Valerio Stephenson, Stacy Ginzler, Ellen M Hanly, John G Tiedge, Henri Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title | Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title_full | Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title_fullStr | Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title_full_unstemmed | Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title_short | Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
title_sort | autoimmune rna dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559755/ https://www.ncbi.nlm.nih.gov/pubmed/36229064 http://dx.doi.org/10.26508/lsa.202201496 |
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